Phase 1 Three Part SAD, MAD & Cross-Over Study of ZP-059 in Healthy and Asthmatic Subjects

NCT04229303 | Completed Phase 1 Results

• 2 other identifiers: Z7240J012019-004031-23
• Study Type: interventional
• Target: 58
• Locations: 1 country
• Sites: 1

Brief Summary

The primary safety objectives were:

• Part 1: To determine the safety and tolerability of single doses of ZP-059 in healthy subjects
• Part 2: To determine the safety and tolerability of multiple doses of ZP-059 in subjects with mild stable asthma
• Part 3: To determine the safety and tolerability of single doses of ZP-059 in subjects with mild to moderate stable asthma. The primary PK objectives were:
• Part 1: To characterize systemic PK of voriconazole and N-oxide voriconazole after single doses of ZP-059 in healthy subjects
• Part 2: To characterize systemic PK of voriconazole and N-oxide voriconazole after multiple doses of ZP-059 in subjects with mild stable asthma
• Part 3: To characterize systemic PK of voriconazole and N-oxide voriconazole after single doses of ZP-059 and single doses of oral voriconazole in subjects with mild to moderate stable asthma.

Conditions

Allergic Bronchopulmonary Aspergillosis

Keywords

ABPA; Asthma; Voriconazole; Allergic Bronchopulmonary Aspergillosis

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Treatment-Emergent Adverse Events (TEAE)

  An AE is any untoward medical occurrence in a patient or clinical study subject, temporally associated with the use of IMP, whether or not considered related to the study IMP.

  Part 1: screening (Day -28 to -1) to follow-up (8 to 12 days after last dose); part 2: screening (Day -28 to -1) to follow-up (11-17 days after last dose); Part 3: screening (Day -28 to -1) to follow-up (8-12 days after last dose of study drug).

Secondary Outcomes (32)

• AUC0-t, AUC0-inf for Voriconazole and N-oxide Voriconazole - Part 1

  Part 1: at day 1 (pre-dose, at 1.5h-2h-3h-4h-12h post dose).

• Cmax for Voriconazole and N-oxide Voriconazole - Part 1

  Part 1: at day 1 (pre-dose, at 1.5h-2h-3h-4h-12h post dose).

• Tmax and T1/2 for Voriconazole and N-oxide Voriconazole - Part 1

  Part 1: at day 1 (pre-dose, at 1.5h-2h-3h-4h-12h post dose).

• Kel for Voriconazole and N-oxide Voriconazole - Part 1

  Part 1: at day 1 (pre-dose, at 1.5h-2h-3h-4h-12h post dose).

• CL/F for Voriconazole - Part 1

  Part 1: at day 1 (pre-dose, at 1.5h-2h-3h-4h-12h post dose).

Study Arms (9)

Part 1 - ZP-059 5mg

EXPERIMENTAL

Part 1: administration of single ascending doses (SAD) of ZP-059. Cohort 1: 5mg (1 x 5 mg capsule) ZP-059 single dose administered via DPI (RS01 monodose device) on Day 1.

Drug: Voriconazole inhaled

Part 1 - ZP-059 10mg

EXPERIMENTAL

Part 1: administration of single ascending doses (SAD) of ZP-059. Cohort 2: 10mg (2 x 5 mg capsule) ZP-059 single dose administered via DPI (RS01 monodose device) on Day 1.

Drug: Voriconazole inhaled

Part 1 - ZP-059 20mg

EXPERIMENTAL

Part 1: administration of single ascending doses (SAD) of ZP-059. Cohort 3: 20mg (4 x 5 mg capsule) ZP-059 single dose administered via DPI (RS01 monodose device) on Day 1.

Drug: Voriconazole inhaled

Part 1 - ZP-059 40mg

EXPERIMENTAL

Part 1: administration of single ascending doses (SAD) of ZP-059. Cohort 4: 40mg (8 x 5 mg capsule) ZP-059 single dose administered via DPI (RS01 monodose device) on Day 1.

Drug: Voriconazole inhaled

Part 2 - ZP-059 10mg bid

EXPERIMENTAL

Part 2: administration of multiple ascending doses (MAD) of ZP-059 on Days 1 to 10. Cohort 1: 10mg (2 x 5 mg capsule) ZP-059 twice daily (bid) administered via DPI (RS01 monodose device) for 9 days and once in the morning of Day 10.

Drug: Voriconazole inhaled

Part 2 - ZP-059 20mg bid

EXPERIMENTAL

Part 2: administration of multiple ascending doses (MAD) of ZP-059 on Day 1 to 10. Cohort 2: 20mg (4 x 5 mg capsule) ZP-059 twice daily (bid) administered via DPI (RS01 monodose device) for 9 days and once in the morning of Day 10.

Drug: Voriconazole inhaled

Part 2 - ZP-059 40mg qd

EXPERIMENTAL

Part 2: administration of multiple ascending doses (MAD) of ZP-059 on Day 1 to 10. Cohort 3: 40mg (8 x 5 mg capsule) ZP-059 once daily (qd) administered via DPI (RS01 monodose device) on Days 1 to 10.

Drug: Voriconazole inhaled

Part 3 - ZP-059 / Oral Voriconazole

EXPERIMENTAL

Crossover treatment period: Single inhaled dose (20 mg) of ZP-059 5mg capsules administered via DPI, and a single dose of oral voriconazole (200 mg Vfend® tablet) on the morning of Day 1 of the respective treatment period with a washout period of at least 96 hours.

Drug: Voriconazole inhaled; Drug: oral voriconazole

Part 3 - Oral Voriconazole / ZP-059

EXPERIMENTAL

Crossover treatment period: Single dose of oral voriconazole (200 mg Vfend® tablet), and a single inhaled dose (20 mg) of ZP-059 5mg capsules administered via DPI on the morning of Day 1 of the respective treatment period with a washout period of at least 96 hours.

Drug: Voriconazole inhaled; Drug: oral voriconazole

Interventions

Voriconazole inhaled DRUG

Part 1 (SAD): eligible subjects received a single ascending inhaled dose (5 mg, 10 mg, 20 mg, and 40 mg) of ZP-059 5mg capsules administered via dry powder inhaler (DPI) on the morning of Day 1. Part 2 (MAD): eligible subjects received 2 (10mg twice daily \[BID\]) or 4 \[20mg BID\]) inhaled doses of ZP-059 5mg capsules administered via DPI BID for 9 days and once in the morning of Day 10, or 8 inhaled doses of ZP-059 5 mg capsules (40mg once daily \[QD\]) for 10 days. For QD dosing, subjects received QD doses of ZP-059 (at hour 0) on Days 1 to 10. Part 3 (2-period crossover): eligible subjects received a 4 \[20mg BID\] inhaled doses of ZP-059 5mg capsules administered via DPI on the morning of Day 1 according to the crossover scheme of the study. ZP-059 (inhaled voriconazole) was provided in clear, colorless size 3 hydroxypropylmethylcellulose hard capsules, which were individually and manually triggered by a breath actuated inhalation device (RS01 monodose inhaler).

Also known as: ZP-059

Part 1 - ZP-059 10mg; Part 1 - ZP-059 20mg; Part 1 - ZP-059 40mg; Part 1 - ZP-059 5mg; Part 2 - ZP-059 10mg bid; Part 2 - ZP-059 20mg bid; Part 2 - ZP-059 40mg qd; Part 3 - Oral Voriconazole / ZP-059; Part 3 - ZP-059 / Oral Voriconazole

oral voriconazole DRUG

Part 3 (2-period crossover): eligible subjects received a single dose of oral voriconazole (200mg oral film-coated tablet, Vfend) on the morning of Day 1 according to the crossover scheme of the study.

Also known as: Vfend

Part 3 - Oral Voriconazole / ZP-059; Part 3 - ZP-059 / Oral Voriconazole

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Female subjects must be either of non-childbearing potential or if of childbearing potential use a highly effective birth control method
• Male subjects with female partners of childbearing potential must be vasectomised with documented medical assessment of the surgical success or use highly effective contraception together with their female partner(s)
• Subject must agree not to donate semen or ova/oocytes during the study and for 14 days after the last dose of IMP.
• BMI ≥ 18.0 and ≤ 35.0 kg/m2 at Screening.
• Are willing and able to comply with all aspects of the protocol.
• FEV1 ≥80% of the predicted value and FEV1/FVC ratio \> 0.70; at screening.
• Able to demonstrate the correct inhalation technique for use of delivery device during the study at screening and pre-dose Day 1.
• Subjects with mild stable asthma with a documented physician confirmed diagnosis of asthma for at least 3 months prior to screening.
• Asthma assessed by investigator as being stable for at least 4 weeks prior to screening and prior to Day 1.
• Female subjects must be either of non-childbearing potential or if of childbearing potential use a highly effective birth control method
• Male subjects with female partners of childbearing potential must be vasectomised with documented medical assessment of the surgical success or use highly effective contraception together with their female partner(s).
• Subject must agree not to donate semen or ova/oocytes during the study and for 14 days after the last dose of IMP.
• Body mass index (BMI) ≥ 18.0 and ≤ 35.0 kg/m2 at Screening.
• Are willing and able to comply with all aspects of the protocol.
• Subject is being treated with short acting beta-agonists alone or in conjunction with low to medium doses of ICS.

You may not qualify if:

• Subjects who are Chinese or Japanese.
• Subjects who have received any IMP in a clinical research study within the previous 3 months prior to Day 1.
• Participation in other interventional studies for the duration of the study.
• Subjects who are study site employees or immediate family members of a study site or sponsor employee.
• History of any drug or alcohol abuse in the past 2 years prior to screening.
• Regular alcohol consumption in males \>21 units per week and females \>14 units per week (1 unit = ½ pint beer, a 25 mL shot of 40% spirit or a 125 mL glass of wine depending on type).
• Current tobacco or marijuana smokers and those who have smoked within the last 12 months prior to screening or prior to Day 1.
• A confirmed positive urine cotinine test at screening or Day -1.
• Current users of e-cigarettes or nicotine replacement products and those who have used these products within the last 12 months prior to screening or prior to Day 1.
• Smoking history of \>5 pack years at screening.
• Females of childbearing potential who are pregnant or lactating, or who plan to become pregnant during the study. A woman is considered of childbearing potential unless she is permanently sterile (hysterectomy, bilateral salpingectomy, bilateral oophorectomy, bilateral tubal occlusion/ligation) or is postmenopausal (had no menses for 12 months without an alternative medical cause).
• Female subject with a positive pregnancy test at screening or pre-dose on Day 1.
• Subjects who do not have suitable veins for multiple venepunctures/cannulation as assessed by the investigator at screening.
• Evidence or history of clinically significant abnormal biochemistry, haematology or urinalysis at screening, as judged by the investigator; the investigator should contact the medical monitor and /or the sponsor if required.
• Positive urine drugs of abuse test or alcohol breath test result at screening or Day -1.

Sponsors & Collaborators

• Zambon SpA: lead

Study Sites (1)

Medicines Evaluation Unit Ltd. (MEU)

Manchester, M239QZ, United Kingdom

Location

Related Publications (1)

• Caponetti G, Sala F, Cervetti A, Colombo D, Tiberio E, Singh D. Phase I Study of the Safety, Tolerability, and Pharmacokinetics of Inhaled Voriconazole in Healthy Volunteers and Subjects With Stable Asthma. Pharmacol Res Perspect. 2025 Feb;13(1):e70064. doi: 10.1002/prp2.70064.

  PMID: 39918069 DERIVED

MeSH Terms

Conditions

Aspergillosis, Allergic Bronchopulmonary; Asthma

Interventions

Voriconazole

Condition Hierarchy (Ancestors)

Pulmonary Aspergillosis; Aspergillosis; Mycoses; Bacterial Infections and Mycoses; Infections; Lung Diseases, Fungal; Respiratory Tract Infections; Lung Diseases; Respiratory Tract Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases; Bronchial Diseases; Lung Diseases, Obstructive

Intervention Hierarchy (Ancestors)

Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Arnd Mueller, MD
• Organization: Zambon SpA

clinicaltrials@zambongroup.com

+39 02 665241

Study Officials

• Sukh Dave Singh, Prof, MD,

  The Medicine Evaluation Unit (MEU) Ltd, Langley building,

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Safety, tolerability and PK will be assessed following either single ascending (SAD) or multiple ascending (MAD) dosing of ZP-059; Part 1 and Part 2, respectively. Part 1 will comprise 4 separate cohorts planned to receive single doses of ZP-059; part 2 will comprise 3 separate cohorts planned to receive daily doses of ZP-059 on Day 1 to 10; part 3 is a 2-period, randomised crossover study in subjects with mild to moderate stable asthma to assess the safety, tolerability and PK of single doses of ZP-059 and single doses of oral voriconazole.

Study Record Dates

• First Submitted: December 6, 2019
• First Posted: January 18, 2020
• Study Start: February 11, 2020
• Primary Completion: August 31, 2020
• Study Completion: August 31, 2020
• Last Updated: November 15, 2021
• Results First Posted: November 15, 2021

Record last verified: 2019-12

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)